Group Max Levin

Research summary

Immunotherapy with immune checkpoint inhibitors induce durable responses and long-term survival in a subset of patients with metastatic melanoma. However, more than half of patients do not respond to therapy. Immunotherapy activate anti-tumor T-cell immunity but can also trigger autoimmune toxicities. Interestingly, certain specific immune toxcities are strongly associated with exceptional and lasting treatment responses, suggesting that these toxicities may reflect immune mechanisms that are critical for effective tumor eradication.

The aim of this project is to identify immune mechanisms underlying response-linked immune toxicities and determine whether these mechanisms can be used to improve the efficacy of immunotherapy in metastatic melanoma.

We analyze blood and tissue samples from immunotherapy-treated patients with and without response-linked immune toxicities. Comprehensive immune profiling is performed using flow cytometry, single-cell RNA sequencing, T-cell receptor clonality analysis, proteomics, and multiplex tissue imaging to identify immune cell subsets, pathways, and biomarkers associated with exceptional responses.

Identifying immune pathways linked to exceptional responses may reveal new therapeutic targets and biomarkers that improve patient selection and help convert non-responders into responders to immunotherapy.

Research tools and resources

We analyze liquid and tissue biopsies from our cohort of patients with metastatic melanoma treated with immune checkpoint inhibitors. Our work focuses on immune trajectories in longitudinal samples collected from selected patients over several years. To achieve this, we apply a broad range of techniques, including flow cytometry, single-cell RNA sequencing, T cell clonality analysis, as well as both targeted and exploratory proteomics and lipidomics.

Current group members

Max Levin, MD, PhD, Professor
Sara Bjursten, MD, PhD, postdoc
Timothy Sundell, PhD, postdoc
Zhiyuan Zhao, MD. PhD, postdoc
Ankur Pandita, MD, PhD student
Maria Lindén, MD, PhD student
Hifaa Al Remawi, MD, PhD student
Rebecca Norrbink, medical student
 

Selected publications

1. PD-1 inhibitor-induced rheumatic, endocrine, and sarcoidosis-like immune-related adverse events in metastatic melanoma are associated with improved survival and lower corticosteroid exposure.
   Lindén M, Al Remawi H, Fager A, Akyürek LM, Rudin A, Ny L, Bjursten S, Pandita A, Levin M.  Immunother Adv. 2026 Feb 21;6(1).
    
2. Immune-related hepatitis and hypophysitis are associated with superior survival in melanoma patients treated with combined ipilimumab and nivolumab.
   Al Remawi H, Lindén M, Zhao Z, Pandita A, Rudin A, Ny L, Bjursten S, Levin M.  Oncoimmunology. 2025. Dec;14(1):2543510.
    
3. Immune mapping of human tuberculosis and sarcoidosis lung granulomas. 
   Carow B, Muliadi V, Skålén K, Yokota C, Kathamuthu GR, Setiabudiawan TP, Lange C, Scheu K, Gaede KI, Goldmann T, Pandita A, Masood KI, Pervez S, Grunewald J, Hasan Z, Levin M, Rottenberg ME. Front Immunol. 2024 Feb 7;14:1332733.
    
4. Concentrations of S100B and neurofilament light chain in blood as biomarkers for checkpoint inhibitor-induced CNS inflammation.
   Bjursten S, Zhao Z, Al Remawi H, Studahl M, Pandita A, Simrén J, Zetterberg H, Lundell AC, Rudin A, Ny L, Levin M.  EBioMedicine. 2024 Feb;100:104955
    
5. Early increase of circulating transitional B cells  and autoantibodies to joint-related proteins in patients with metastatic melanoma developing  checkpoint inhibitor-induced inflammatory arthritis.
   Gatto M, Bjursten S, Jonsson CA, Leu Agelii M, Jonell C, McGrath S, Lönnblom E, Sareila  O, Holmdahl R, Rudin A, Levin M*, Gjertsson I.* Arthritis Rheumatol. 2022 Nov 21. *shared senior authors
    
6. Intussusceptive Angiogenesis in Human Metastatic Malignant Melanoma.
   Pandita A, Ekstrand M, Bjursten S, Zhao Z, Fogelstrand P, Le Gal K, Ny L, Bergö MO,  Karlsson J, Nilsson JA, Akyürek LM, Levin MC, Borén J, Ewald AJ, Mostov KE, Levin M. Am J Pathol. 2021 Nov;191(11):2023-2038. 
    
7. Early rise in brain damage markers and high  ICOS expression in CD4+ and CD8+ T cells during checkpoint inhibitor-induced encephalomyelitis.
   Bjursten S, Pandita A, Zhao Z, Fröjd C, Ny L, Jensen C, Ullerstam T, Jespersen H, Borén  J, Levin MC, Zetterberg H, Rudin A, Levin M.  J Immunother Cancer. 2021 Jul;9(7):e002732.  
    
8. Dynamic ctDNA evaluation of a patient with BRAFV600E metastatic melanoma demonstrates the utility of  ctDNA for disease monitoring and tumor clonality analysis.
   Vannas C, Bjursten S, Filges S, Fagman H, Ståhlberg A, Levin M. Acta Oncol. 2020; Nov;59(11):1388- 1392.  
    
9. Checkpoint inhibitor-induced sarcoid reaction mimicking bone metastases.
   Jespersen H,  Bjursten S, Ny L, Levin M. Lancet Oncol. 2018 Jun;19(6):e327  

More group Max Levin publications on PubMed